World production and consumption of aldehydes and other oxo-chemicals was nearly 9.6 million metric tons in 2005. Global capacity utilization increased to 84% in 2005 from 79% in 2001 as a result of stronger demand, increased production and rationalized capacity. Between 2001 and 2005, world capacity for aldehydes and other oxo-chemicals grew at an average annual rate of 1.6%, a lower rate than world consumption, which grew at an average annual rate of 3.4% during the same period.
Most commonly, aldehydes and other oxo-chemicals are currently being produced by refinery methods using petrochemicals derived from crude oil cracking. For example, C3 to C15 aldehydes are generated via hydroformylation of olefins with synthesis gas, and the so produced aldehydes are then converted to corresponding alcohols, acids, or other derivatives. Currently, the oxo-chemical in highest demand is n-butyraldehyde, followed by C6-C13 aldehydes for plasticizer alcohols, and isobutyraldehyde and C12-C18 aldehydes for detergent alcohols.
Microbial synthesis of biofuels using metabolically engineered microbial cells, and especially production of C2-C6 alcohols is well known in the art. For example, microbial ethanol production from carbohydrates is described in WO 94/06924 and ethanol production from CO2 is reported in U.S. Pat. No. 8,048,666. Short-chain alcohol production from 2-keto acids using metabolically engineered cells is described in U.S. Pat. App. No. 2009/0081746, and numerous publications are directed to isobutanol production from metabolically engineered cells (e.g., U.S. Pat. Nos. 7,851,188 and 7,993,889, and in WO 2009/086423, WO 2009/149240, WO 2010/062597, and WO 2010/075504), and alcohol production from CO2 using photosynthetically active organisms is described in US2011/0250660. Similar methods were also described by Kechun Zhang et al. in Proc. Nat. Acad. Sci. (2008), 105, no. 52: 20653-20658. C5-8 alcohol production from 2-keto acids using metabolically engineered cells was described in U.S. Pat. App. No. 2011/0201083, and production of fatty aldehydes from various carbon sources was reported in U.S. Pat. No. 8,097,439. These and all other extrinsic materials discussed herein are incorporated by reference in their entirety. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.
Unfortunately, yield of alcohol using many of such processes is still relatively low. To improve yield of at least certain alcohols, endogenous alcohol dehydrogenases can be deleted or suppressed, and can be replaced with a recombinant dehydrogenase as described in WO 2009/149240A1. While such modifications are often desirable to at least some extent, other problems arise. For example, various alcohols are toxic to the cells producing the alcohol above a threshold concentration, which tends to limit the overall yield. Moreover, most microbially synthesized alcohols are completely miscible with the fermentation medium and need a rather energy consuming process for isolation. Worse, yet, some of the alcohols for azeotropic mixtures and are even more difficult to separate from the medium.
Thus, even though numerous systems and methods of production of aldehydes, oxo-chemicals, and corresponding alcohols are known in the art, several difficulties nevertheless remain. Therefore, there is still a need for improvement, particularly where such chemicals are produced using a microbial system.